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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. Selective impairment of endothelium-dependent relaxation has been demonstrated in aortas of both nondiabetic animals exposed to elevated concentrations of glucose in vitro and insulin-dependent diabetic animals. The impaired NO release in experimentally induced diabetes may be prevented by a number of antioxidants. It has been hypothesized that oxygen-derived free radicals (OFR) generated during both glucose autoxidation and formation of advanced glycosylation end products may interfere with NO action and attenuate its vasodilatory activity. The oxidative injury may also be increased in diabetes mellitus because of a weakened defense due to reduced endogenous antioxidants (vitamin E, reduced glutathione [GSH]). A defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of NO or increased production of free radicals, mainly superoxide anion, may facilitate the development of an arterial functional spasm. Treatment with different antioxidants increases blood flow in the forearm and decreases blood pressure and viscosity in normal humans; vitamin E inhibits nonenzymatic glycosylation, oxidative stress, and red blood cell microviscosity in diabetic patients. Long-term randomized clinical trials of adequate size in secondary and primary prevention could support the free-radical hypothesis for diabetic diabetic vascular complications and the use of antioxidants to reduce the risk of coronary heart disease.
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PMID:Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? 788 82

Free radicals are produced in the body as by products of normal metabolism and as a result of exposure to radiation and some environmental pollutants. Because they are highly reactive, they can damage cellular components and are implicated in a variety of diseases. Free radicals are normally neutralized by efficient systems in the body that include the antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and the nutrient-derived antioxidant small molecules (vitamin E, vitamin C, carotenes, flavonoids, glutathione, uric acid, and taurine). In healthy individuals, a delicate balance exists between free radicals and antioxidants. In some pathologic conditions such as diabetes, and in critically ill patients, oxidative stress causes the level of antioxidants to fall below normal. Antioxidant supplements for such conditions are expected to be of benefit. As a preventive measure against certain diseases, the best approach for healthy individuals is to regularly consume adequate amounts of antioxidant-rich foods, eg, fruits and vegetables.
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PMID:Role of antioxidants in health maintenance. 789 13

Several factors contribute to increased vascular permeability in diabetes mellitus, namely hyperglycaemia leading to increased production of diacylglycerol and thence protein kinase C, non-enzymatic glucosylation generating free radicals and lipid peroxides, sorbitol formation, loss of endothelial cell surface heparan sulphates, and the action of arachidonate derivatives that affect endothelial cell contractility. In view of the importance of oxidative damage, serious consideration must be given to therapeutic regimens that utilise vitamin E or ascorbic acid or D-myoinositol. Probucol is an available antioxidant whose properties have received insufficient attention. The oleate of monounsaturated oil diets is likewise anti-oxidant. Furthermore there is a possibility of replacing lost surface heparan sulphates.
Diabetes Res Clin Pract 1994 Apr
PMID:Vascular permeability in diabetics and implications for therapy. 792 72

Hyperglycemia and diabetes have been shown to increase diacylglycerol (DAG) level and activate protein kinase C (PKC) activity in the vascular tissues, possibly altering vascular function. We have characterized the effects of D-alpha-tocopherol (vitamin E) on PKC activities and DAG levels in rat aortic smooth muscle cells (ASMCs) cultured with elevated glucose levels as well as in the vascular tissues obtained from control and diabetic rats. In ASMCs, the specific PKC activity from the membraneous fraction and total DAG level were increased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/l. The addition of D-alpha-tocopherol and another lipophilic antioxidant, probucol, prevented the glucose-stimulated increases in DAG level and PKC activity. By immunoblotting studies, D-alpha-tocopherol treatment was able to reduce the enhancement of PKC beta II isoform in the membraneous fraction isolated from ASMCs. Comparing streptozotocin-induced diabetic rats with their nondiabetic controls, both membraneous-specific PKC activities and total cellular DAG levels were increased in aorta by 162% (P < 0.05) and 60% (P < 0.05), respectively. Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day prevented the increases in membraneous-specific PKC activities and total DAG levels in parallel with a significant increase of D-alpha-tocopherol contents in the aorta and plasma. These findings have demonstrated that D-alpha-tocopherol can prevent the activation of PKC activities in the vascular cells and tissues induced by hyperglycemia by lowering DAG levels, possibly via its antioxidant effect.
Diabetes 1994 Nov
PMID:Normalization of diacylglycerol-protein kinase C activation by vitamin E in aorta of diabetic rats and cultured rat smooth muscle cells exposed to elevated glucose levels. 792 14

The authors have investigated the state of lipid peroxidation in 118 patients having purulent wounds of soft tissues against the background of diabetes mellitus. It was shown that the parenteral administration of vitamin E and the intracorporeal UVI of blood accelerated the process of stabilization of the parameters of lipid peroxidation and shortened the time of treatment. A combination of these two medical factors included in the complex of curative measures proved to be most effective.
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PMID:[The possibilities for correcting lipid peroxidation in suppurative wounds in diabetic patients]. 797 34

The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.
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PMID:[Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]. 800 9

This study was performed to determine whether vitamin E supplementation in streptozotocin-induced diabetic rats treated by insulin could reduce serum oxidation markers (malondialdehyde: MDA, Schiff bases, anti-protein-MDA adduct antibodies) and modulate lipid changes. After 10 weeks, diabetes induced in rats a significant increase in Schiff bases (P < 0.006) and anti-protein-MDA adduct antibodies (P < 0.01). These alterations were accompanied by a significant rise in serum free fatty acids (225%), triglycerides (35%), and phospholipids (30%) and changes in fatty acid distribution in these fractions and in cholesterol esters. Vitamin E supplementation in diabetic rats reduced Schiff bases and anti-protein-MDA adduct antibodies and tended to restore the fatty acid profile close to control rats without decreasing quantitatively serum lipids enhanced by diabetes. Concerning fatty acids, vitamin E chiefly reduced stearic acid (C18:0) in free fatty acids, cholesterol esters, and phospholipids and cancelled the decrease in low molecular triglycerides observed in diabetic rats. Furthermore, vitamin E maintained the ratio of monounsaturated and polyunsaturated fatty acids, particularly with respect to oleic acid (C18:1), dihomo-gamma-linolenic acid (C20:3 n-6), eicosapentaenoic (C20:5 n-3), and docosapentaenoic acid (C22:5 n-3), in serum phospholipids. These changes observed in vitamin E supplemented rats, compared to vitamin E-untreated diabetic rats, could favor prevention of accelerated atherogenesis. Particularly, the decrease of serum peroxides and enhancement in phospholipid fatty acids (C20:3 n-6, C20:5 n-3, and C22:5 n-3) could induce the preferential formation of prostaglandins (PGE1, PGI2, PGI3) which are protective in cardiovascular diseases.
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PMID:High dosage vitamin E effect on oxidative status and serum lipids distribution in streptozotocin-induced diabetic rats. 812 91

Premature atherosclerosis and other vascular disorders are serious complications of diabetes mellitus. Contributing factors include (i) increased peroxidation of LDL leading to foam cell formation, fatty streaks and plaque formation in the arterial wall, and (ii) hyperreactivity of blood platelets leading to increased platelet adhesion and aggregation. Vitamin E may play a protective role as an antioxidant and/or membrane stabilizing agent in either mechanism. In platelets it appears to regulate arachidonic acid metabolism. Decreased vitamin E levels in platelets are associated with increased aggregation. This is reversible by correction of the vitamin E status. In diabetics, platelet vitamin E levels tend to be reduced with concomitant increase in platelet aggregation. Several studies in patients with insulin-dependent diabetes mellitus and, to some extent, in those with non-insulin-dependent diabetes mellitus have shown that supplementation with several hundred IU vitamin E significantly reduced platelet aggregation and lipid peroxidation. In healthy volunteers high-dose supplementation had no notable effect on platelet aggregation. However, doses as low as 200 IU vitamin E significantly reduced platelet adhesion and inhibited the formation of protruding pseudopods typically occurring in activated platelets. In diabetic patients a decrease in the nonenzymatic glycation of proteins by vitamin E supplementation has been observed. Controlled studies are needed to confirm the effect of vitamin E on platelet function in well-defined groups of diabetics, followed by large-scale trials investigating the prevention of diabetic vascular complications as clinical end point.
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PMID:Prevention of platelet dysfunction by vitamin E in diabetic atherosclerosis. 812 46

The vascular endothelium is the site of formation of several powerful mediators. One of these is NO, a chemically unstable radical formed by enzymatic conversion of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion and aggregation. The biological actions of NO make it a key substance in the endogenous defense against vascular occlusion and thrombosis. The basal formation of NO maintains a moderate but significant vasodilation in the systemic resistance vessels and counteracts platelet activity. When blood flow in conduit arteries is increased there is an augmented endothelial formation of NO, eliciting flow-dependent vasodilation. Beside this, several vasodilators (acetylcholine, bradykinin, histamine, substance P) operate by stimulating endothelial NO formation. On the other hand, drugs like nitroglycerin and papaverine operate independently of the vascular endothelium. Vasodilator mechanisms, physiological as well as pharmacological, may therefore be characterized as endothelium-dependent (i.e. NO-mediated), or endothelium-independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur. Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be due to decreased formation, increased degradation, decreased sensitivity to the NO formed, or a mixture of these factors. Irrespective of the mechanism behind, this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in several cardiovascular settings, like atherosclerosis, hypercholesterolaemia, diabetes, and essential hypertension. Endothelial dysfunction leads to an impaired tissue perfusion, increased local vascular resistance, decreased defense against thrombus formation, and possibly also decreased defense against hypertrophy of the VSMC in the vessel wall media. In patients with CHD, endothelial dysfunction leads to an impaired coronary flow response to physical and mental stress, and to promotion of platelet adherence and aggregability. Endothelial dysfunction is thereby a probable aggravating factor in the atherosclerotic process, adding a functional component on top of the structural lesions characterizing this disease. A particular form of endothelial dysfunction, limited to the arterial resistance vessels, may explain the symptoms and clinical characteristics of microvascular angina. In patients with essential hypertension, endothelial dysfunction prevails, adding a functional component to the structural factors also in this disease. Hitherto, the only therapeutic tools available to restore endothelial dysfunction appear to be restriction of the dietary intake of lipids, possibly reinforced with intake of antioxidants like fish oil and vitamin E. However, large clinical trials to confirm the efficacy of such therapy in reversing endothelial dysfunction have not been conducted. In the future, more directly acting therapeutic regimens, aimed at supporting or substituting the endogenous formation of NO, are likely to appear as well.
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PMID:Endothelial nitric oxide and cardiovascular disease. 815 Dec 63

Studies indicate that large doses of all-rac-alpha-tocopherol in people with diabetes or ascorbic acid in nondiabetic subjects reduces protein glycosylation. The mechanisms by which these nutrients influence glycosylation are poorly understood but may be related to their ability to function as antioxidants. We examined the relationship between glycosylated hemoglobin (GHb) and intake of vitamins E and C and beta-carotene in a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study. In people with diabetes, no significant associations were observed between GHb and intake of vitamins E and C and beta-carotene. In people without diabetes, energy-adjusted vitamin C intake was negatively associated with GHb after age and sex were controlled for (dietary, P = 0.02; total, P = 0.04). No significant relationships between GHb and intake of vitamin E and beta-carotene were observed.
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PMID:Glycosylated hemoglobin concentrations and vitamin E, vitamin C, and beta-carotene intake in diabetic and nondiabetic older adults. 823 54


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